Genetic evidence for serum amyloid P component as a drug target in neurodegenerative disorders.

The mechanisms responsible for neuronal death causing cognitive loss in Alzheimer's disease (AD) and many other dementias are not known. Serum amyloid P component (SAP) is a constitutive plasma protein, which is cytotoxic for cerebral neurones and also promotes formation and persistence of cerebral Aß amyloid and neurofibrillary tangles. Circulating SAP, which is produced exclusively by the liver, is normally almost completely excluded from the brain. Conditions increasing brain exposure to SAP increase dementia risk, consistent with a causative role in neurodegeneration. Furthermore, neocortex content of SAP is strongly and independently associated with dementia at death. Here, seeking genomic evidence for a causal link of SAP with neurodegeneration, we meta-analysed three genome-wide association studies of 44 288 participants, then conducted cis-Mendelian randomization assessment of associations with neurodegenerative diseases. Higher genetically instrumented plasma SAP concentrations were associated with AD (odds ratio 1.07, 95% confidence interval (CI) 1.02; 1.11, p = 1.8 × 10-3), Lewy body dementia (odds ratio 1.37, 95%CI 1.19; 1.59, p = 1.5 × 10-5) and plasma tau concentration (0.06 log2(ng l-1) 95%CI 0.03; 0.08, p = 4.55 × 10-6). These genetic findings are consistent with neuropathogenicity of SAP. Depletion of SAP from the blood and the brain, by the safe, well tolerated, experimental drug miridesap may thus be neuroprotective.

Serum amyloid P component: Structure, biological activity, and application in diagnosis and treatment of immune-associated diseases.

Serum amyloid P component (SAP) is a member the innate immune humoral arm and participated in various processes, including the innate immune responses, tissue remodeling, and the pathogenesis of inflammatory diseases. Remarkably, SAP is a highly versatile immunomodulatory factor that can serve as a drug target for treating amyloid diseases and reduce inflammation, fibrosis degree, and respiratory disease. In this review, we focus on the biological activities of SAP and its application in different systemic immune-associated diseases. First, we reviewed the regulatory effects of SAP on innate immune cells and possible mechanisms. Second, we emphasized SAP as a diagnostic marker and therapeutic target for immune-associated diseases, including the neuropsychiatric disorders. Third, we presented several recommendations for regulating SAP in immune cell function and potential areas for future research. Some authorities consider SAP to be a pattern recognition molecule that plays multiple roles in the innate immune system and inflammation. Developing therapeutics that target SAP or its associated signaling pathways may be a promising strategy for treating immune-associated diseases.

Serum amyloid P component accumulates and persists in neurones following traumatic brain injury.

The mechanisms underlying neurodegenerative sequelae of traumatic brain injury (TBI) are poorly understood. The normal plasma protein, serum amyloid P component (SAP), which is normally rigorously excluded from the brain, is directly neurocytotoxic for cerebral neurones and also binds to Aß amyloid fibrils and neurofibrillary tangles, promoting formation and persistence of Aß fibrils. Increased brain exposure to SAP is common to many risk factors for dementia, including TBI, and dementia at death in the elderly is significantly associated with neocortical SAP content. Here, in 18 of 30 severe TBI cases, we report immunohistochemical staining for SAP in contused brain tissue with blood-brain barrier disruption. The SAP was localized to neurofilaments in a subset of neurones and their processes, particularly damaged axons and cell bodies, and was present regardless of the time after injury. No SAP was detected on astrocytes, microglia, cerebral capillaries or serotoninergic neurones and was absent from undamaged brain. C-reactive protein, the control plasma protein most closely similar to SAP, was only detected within capillary lumina. The appearance of neurocytotoxic SAP in the brain after TBI, and its persistent, selective deposition in cerebral neurones, are consistent with a potential contribution to subsequent neurodegeneration.

Genetic evidence for serum amyloid P component as a drug target for treatment of neurodegenerative disorders.

The direct causes of neurodegeneration underlying Alzheimer's disease (AD) and many other dementias, are not known. Here we identify serum amyloid P component (SAP), a constitutive plasma protein normally excluded from the brain, as a potential drug target. After meta-analysis of three genome-wide association studies, comprising 44,288 participants, cis-Mendelian randomization showed that genes responsible for higher plasma SAP values are significantly associated with AD, Lewy body dementia and plasma tau concentration. These genetic findings are consistent with experimental evidence of SAP neurotoxicity and the strong, independent association of neocortex SAP content with dementia at death. Depletion of SAP from the blood and from the brain, as is provided by the safe, well tolerated, experimental drug, miridesap, may therefore contribute to treatment of neurodegeneration.

Serum Amyloid P Attenuates Hypertrophic Scarring in Large Animal Models.

INTRODUCTION: This study's purpose was to (1)determine the effect of locally administered serum amyloid P (SAP) on the development of hypertrophic scars (HTS) in porcine and rabbit HTS models and (2)determine the pharmacokinetics of systemically administered SAP and its effect on circulating fibrocyte quantities. METHODS: Two large animal (New Zealand White Rabbit and Female Red Duroc Pigs) HTS models were utilized to study the effects of daily local injections of SAP immediately post wounding (x5 d in rabbits; x7 d in pigs) on HTS development as measured by scar elevation index , scar area, wound closure, and molecular expression studies of scar components. For SAP pharmacokinetics, total and human SAP levels in porcine blood were measured at regular intervals following intravenous administration of human SAP. Fibrocyte quantities were determined prior to and 1 h following human SAP intravenous administration. RESULTS: In the rabbit model, local SAP significantly decreased the level of tissue inhibitor of metalloproteinases-1 mRNA expression and maintained matrix mettaloproteinase-9 expression, while control and vehicle groups significantly declined. In the pig model, there was a significant decrease in the trend of scar elevation indexes treated with local SAP versus controls over the study period. This decrease was statistically significant at days 14 and 84. Human SAP administered intravenously is degraded within 24 h and does not influence circulating fibrocyte quantities. CONCLUSIONS: This is the first study to demonstrate attenuation of HTS formation using locally administered SAP in large animal HTS models. Local SAP administration reduces HTS formation by maintaining matrix mettaloproteinase-9 and decreasing tissue inhibitor of metalloproteinases-1. Intravenous administration of SAP is not as effective.

SAP deficiency aggravates periodontitis possibly via C5a-C5aR signaling-mediated defective macrophage phagocytosis of Porphyromonas gingivalis.

INTRODUCTION: Serum amyloid P component (SAP) regulates the innate immune system and microbial diseases. Periodontitis is an inflammatory oral disease developed by the host immune system's interaction with the dysbiotic oral microbiome, thereby SAP could play a role in periodontitis pathogenicity. OBJECTIVES: To investigate the role of SAP in oral microbiome modulation and peridontitis pathogenicity. METHODS: In this study, wildtype and SAP-knockout (KO) mice were used. Ligature-based periodontitis was developed in mice. Oral microbiome diversity was analyzed by 16 s rRNA sequencing. Macrophages and Porphyromonas gingivalis (P. gingivalis) co-culture system analyzed the effect of SAP in macrophage phagocytosis of P. gingivalis. RESULTS: The level of SAP was upregulated in the periodontitis-affected periodontium of humans and mice but not in the liver and blood circulation. Periodontal macrophages were the key source of upregulated SAP in periodontitis. SAP-KO aggravated periodontal inflammation, periodontitis, and a higher number of M1-type inflammatory macrophage infiltration in the periodontium. The oral microbiome of SAP-KO periodontitis mice was altered with a higher abundance of Porphyromonas at the genus level. SAP-KO macrophages showed compromised phagocytosis of P. gingivalis in the co-culture system. Co-culture of SAP-KO macrophages and P. gingivalis induced the C5a expression and exogenous SAP treatment nullified this effect. Exogenous recombinant SAP treatment did not affect P. gingivalis growth and opsonization. PMX205, an antagonist of C5a, treatment robustly enhanced P. gingivalis phagocytosis by SAP-KO macrophages, indicating the involvement of the C5a-C5aR signaling in the compromised P. gingivalis phagocytosis by SAP-KO macrophages. CONCLUSION: SAP deficiency aggravates periodontitis possibly via C5a-C5aR signaling-mediated defective macrophage phagocytosis of P. gingivalis. A higher abundance of P. gingivalis during SAP deficiency could promote M1 macrophage polarization and periodontitis. This finding suggests the possible protecting role of elevated levels of periodontal SAP against periodontitis progression.

The Paradoxical Effects of Serum Amyloid-P Component on Disseminated Candidiasis.

Serum amyloid P component (SAP) may play an important role in human fungal diseases. SAP binds to functional amyloid on the fungal surface and masks fungi from host immune processes, skewing the macrophage population from the pro-inflammatory M1 to the quiescent M2 type. We assessed the role of SAP in a murine model of disseminated candidiasis. Mice were injected with human SAP subcutaneously (SQ) followed by intravenous injection of Candida albicans. Male, BALBcJ mice were administered 2 mg human SAP or the homologous human pro-inflammatory pentraxin CRP, SQ on day −1 followed by 1 mg on days 0 thru 4; yeast cells were administered intravenously on day 0. Mice not receiving a pentraxin were morbid on day 1, surviving 4−7 days. Mice administered SAP survived longer than mice receiving yeast cells alone (p < 0.022), although all mice died. Mice given CRP died faster than mice receiving yeast cells alone (p < 0.017). Miridesap is a molecule that avidly binds SAP, following which the complex is broken down by the liver. Miridesap administered in the drinking water removed SAP from the serum and yeast cells and significantly prolonged the life of mice (p < 0.020). Some were "cured" of candidiasis. SAP administered early in the septic process provided short-lived benefit to mice, probably by blunting cytokine secretion associated with disseminated candidiasis. The most important finding was that removal of SAP with miridesap led to prolonged survival by removing SAP and preventing its dampening effects on the host immune response.

Clinicopathologic characteristics of pancreatic islet amyloidosis in the rhesus macaque (Macaca mulatta) and sooty mangabey (Cercocebus atys).

BACKGROUND: Diabetes mellitus type 2 has been linked to pancreatic islet amyloid deposition in humans and nonhuman primates. The authors hypothesized that diabetic primates would have significant differences in pathology than non-diabetic groups. METHODS: This retrospective study used histopathology and immunohistochemistry to characterize and compare pancreatic islet amyloidosis in 58 diabetic and non-diabetic rhesus macaque (RM) and sooty mangabeys (SM). RESULTS: The pancreatic tissues from diabetic RM and SM showed higher histopathology scores for islet amyloid deposit distribution, severity, and calcification deposits compared to their respective non-diabetic cohorts. Further, these tissues from RM and SM with amyloid deposits showed immunoreactivity to insulin, glucagon, islet amyloid polypeptide, serum amyloid P, and glucagon-like peptide 1. CONCLUSIONS: Histopathology results showed that the defined amyloid characteristics are associated with clinical diabetes in both species. The immunohistochemistry results collectively suggest differences in pancreatic hormones and islet amyloid components among both species and diabetic status.

Pharmacodynamic evaluation and safety assessment of treatment with antibodies to serum amyloid P component in patients with cardiac amyloidosis: an open-label Phase 2 study and an adjunctive immuno-PET imaging study.

BACKGROUND: In a Phase I study treatment with the serum amyloid P component (SAP) depleter miridesap followed by monoclonal antibody to SAP (dezamizumab) showed removal of amyloid from liver, spleen and kidney in patients with systemic amyloidosis. We report results from a Phase 2 study and concurrent immuno-positron emission tomography (PET) study assessing efficacy, pharmacodynamics, pharmacokinetics, safety and cardiac uptake (of dezamizumab) following the same intervention in patients with cardiac amyloidosis. METHODS: Both were uncontrolled open-label studies. After SAP depletion with miridesap, patients received ≤ 6 monthly doses of dezamizumab in the Phase 2 trial (n = 7), ≤ 2 doses of non-radiolabelled dezamizumab plus [89Zr]Zr-dezamizumab (total mass dose of 80 mg at session 1 and 500 mg at session 2) in the immuno-PET study (n = 2). Primary endpoints of the Phase 2 study were changed from baseline to follow-up (at 8 weeks) in left ventricular mass (LVM) by cardiac magnetic resonance imaging and safety. Primary endpoint of the immuno-PET study was [89Zr]Zr-dezamizumab cardiac uptake assessed via PET. RESULTS: Dezamizumab produced no appreciable or consistent reduction in LVM nor improvement in cardiac function in the Phase 2 study. In the immuno-PET study, measurable cardiac uptake of [89Zr]Zr-dezamizumab, although seen in both patients, was moderate to low. Uptake was notably lower in the patient with higher LVM. Treatment-associated rash with cutaneous small-vessel vasculitis was observed in both studies. Abdominal large-vessel vasculitis after initial dezamizumab dosing (300 mg) occurred in the first patient with immunoglobulin light chain amyloidosis enrolled in the Phase 2 study. Symptom resolution was nearly complete within 24 h of intravenous methylprednisolone and dezamizumab discontinuation; abdominal computed tomography imaging showed vasculitis resolution by 8 weeks. CONCLUSIONS: Unlike previous observations of visceral amyloid reduction, there was no appreciable evidence of amyloid removal in patients with cardiac amyloidosis in this Phase 2 trial, potentially related to limited cardiac uptake of dezamizumab as demonstrated in the immuno-PET study. The benefit-risk assessment for dezamizumab in cardiac amyloidosis was considered unfavourable after the incidence of large-vessel vasculitis and development for this indication was terminated. Trial registration NCT03044353 (2 February 2017) and NCT03417830 (25 January 2018).

Structural characterization of immune receptor family short pentraxins, C-reactive protein and serum amyloid P component, in primates.

The short pentraxins C-reactive protein (CRP) and serum amyloid P component (SAP) are a family of pattern-recognition molecules that play versatile roles in innate immunity and inflammation. A comprehensive description is currently lacking as to the genetic characteristics of these molecules in primates. In the present study, we analyzed genetic changes of CRP and SAP genes in this phylogenic lineage. The results revealed that adaptive selection has brought about interspecific diversities of both genes. The adaptively selected amino acid changes have occurred in or adjacent to the structural domains involved in ligand- and effector-binding and homologous aggregation. Each gene, however, exhibits a striking lack of genetic variation in both commonly-used non-human primate models Macaca fascicularis and M. mulatta. These findings highlight basic facts on the genetic characteristics of primate short pentraxins and would contribute powerfully to the extrapolation of their functional insights and physiological outcomes from primate models to humans.

Serum amyloid P component level is associated with clinical response to escitalopram treatment in patients with major depressive disorder.

Serum amyloid P component (SAP) is a universal constituent of human amyloid deposits, which has been implicated in Alzheimer's disease and major depressive disorder (MDD). However, the relationship between SAP level and depression severity remains obscure. The aims of this study were to investigate how SAP is involved in depression and to explore the association between SAP level and antidepressant treatment response. Patients with MDD (n = 85) who received escitalopram monotherapy for 8-12 weeks were selected from a multicenter open-label randomized clinical trial. The same number of healthy controls was recruited. Depression severity was measured according to the Hamilton Depression Rating Scale (HAMD-17) at baseline and weeks 4, 8, and 12. The plasma levels of SAP were measured at baseline, week 2 and week 12. As a result, baseline levels of SAP were significantly higher in depressed patients than in control subjects (p < 0.001). SAP levels at baseline were negatively associated with depression severity after escitalopram treatment (p < 0.05), and the changes in SAP levels from baseline to week 12 were highly correlated with the severity of depressive symptoms based on the HAMD-17 score (p < 0.05). Interestingly, treatment with escitalopram significantly decreased the plasma levels of SAP in females, but not in males. Altogether, our results suggest that SAP not only involved in the pathobiology of depression but also mediates the action of antidepressant medications.

Different response of Acipenser gueldenstaedtii CRP/SAP and SAA to bacterial challenge and chronic thermal stress sheds light on the innate immune system of sturgeons.

Sturgeons are chondrostean fish critically endangered due to anthropogenic loss and degradation of natural habitat and overfishing for meat and caviar production. Consequently, sturgeon aquaculture has extensively developed lately, being Russian sturgeon (Acipenser gueldenstaedtii) the second most important species reared for caviar production. However, Russian sturgeon aquaculture in subtropical countries, such as Uruguay, confronts difficulties because fish have to endure excessive summertime warm temperatures, which weaken their innate defences facilitating opportunistic infections. To address this problem, we look for identifying putative acute phase proteins (APPs), which might be robust serum biomarkers of both infection and chronic thermal stress, applied to monitoring Russian sturgeon health status in farms. We focused on the C-Reactive Protein/Serum Amyloid P (CRP/SAP) pentraxin since the pentraxin family includes well-known APPs, better characterised in mammals than fish. We identified A.gueldenstaedtii CRP/SAP (AgCRP/SAP), as a member of the universal CRP/SAP pentraxin sub-family, and studied AgCRP/SAP involvement in sturgeon response to bacterial challenge and chronic thermal stress, in comparison with A. gueldenstaedtii Serum Amyloid A (AgSAA), a previously described positive APP. Results showed that AgCRP/SAP is a constitutive serum component that remained constant upon Aeromonas hydrophila challenge and chronic thermal stress. Contrastingly, serum AgSAA was subjected to regulation by bacterial and thermal stress challenges, showing a 50-fold increase and 3-fold decline in serum levels, respectively. Overall, results highlight the potential value of AgSAA, but not of AgCRP/SAP, as a biomarker of bacterial infection and the need to continue searching for robust chronic thermal stress biomarkers in sturgeons.

Inhibitors of the Sialidase NEU3 as Potential Therapeutics for Fibrosis.

Fibrosing diseases are a major medical problem, and are associated with more deaths per year than cancer in the US. Sialidases are enzymes that remove the sugar sialic acid from glycoconjugates. In this review, we describe efforts to inhibit fibrosis by inhibiting sialidases, and describe the following rationale for considering sialidases to be a potential target to inhibit fibrosis. First, sialidases are upregulated in fibrotic lesions in humans and in a mouse model of pulmonary fibrosis. Second, the extracellular sialidase NEU3 appears to be both necessary and sufficient for pulmonary fibrosis in mice. Third, there exist at least three mechanistic ways in which NEU3 potentiates fibrosis, with two of them being positive feedback loops where a profibrotic cytokine upregulates NEU3, and the upregulated NEU3 then upregulates the profibrotic cytokine. Fourth, a variety of NEU3 inhibitors block pulmonary fibrosis in a mouse model. Finally, the high sialidase levels in a fibrotic lesion cause an easily observed desialylation of serum proteins, and in a mouse model, sialidase inhibitors that stop fibrosis reverse the serum protein desialylation. This then indicates that serum protein sialylation is a potential surrogate biomarker for the effect of sialidase inhibitors, which would facilitate clinical trials to test the exciting possibility that sialidase inhibitors could be used as therapeutics for fibrosis.

ATTR Amyloidosis: Current and Emerging Management Strategies: JACC: CardioOncology State-of-the-Art Review.

Transthyretin cardiac amyloidosis (ATTR-CA) is increasingly diagnosed owing to the emergence of noninvasive imaging and improved awareness. Clinical penetrance of pathogenic alleles is not complete and therefore there is a large cohort of asymptomatic transthyretin variant carriers. Screening strategies, monitoring, and treatment of subclinical ATTR-CA requires further study. Perhaps the most important translational triumph has been the development of effective therapies that have emerged from a biological understanding of ATTR-CA pathophysiology. These include recently proven strategies of transthyretin protein stabilization and silencing of transthyretin production. Data on neurohormonal blockade in ATTR-CA are limited, with the primary focus of medical therapy on judicious fluid management. Atrial fibrillation is common and requires anticoagulation owing to the propensity for thrombus formation. Although conduction disease and ventricular arrhythmias frequently occur, little is known regarding optimal management. Finally, aortic stenosis and ATTR-CA frequently coexist, and transcatheter valve replacement is the preferred treatment approach.

Dementia in the older population is associated with neocortex content of serum amyloid P component.

Despite many reported associations, the direct cause of neurodegeneration responsible for cognitive loss in Alzheimer's disease and some other common dementias is not known. The normal human plasma protein, serum amyloid P component, a constituent of all human fibrillar amyloid deposits and present on most neurofibrillary tangles, is cytotoxic for cerebral neurones in vitro and in experimental animals in vivo. The neocortical content of serum amyloid P component was immunoassayed in 157 subjects aged 65 or more with known dementia status at death, in the large scale, population-representative, brain donor cohort of the Cognitive Function and Ageing Study, which avoids the biases inherent in studies of predefined clinico-pathological groups. The serum amyloid P component values were significantly higher in individuals with dementia, independent of serum albumin content measured as a control for plasma in the cortex samples. The odds ratio for dementia at death in the high serum amyloid P component tertile was 5.24 (95% confidence interval 1.79-15.29) and was independent of Braak tangle stages and Thal amyloid-ß phases of neuropathological severity. The strong and specific association of higher brain content of serum amyloid P component with dementia, independent of neuropathology, is consistent with a pathogenetic role in dementia.

Serum amyloid P component: a new biomarker for low sperm concentration?

Serum amyloid P component (SAP) is present in seminal plasma, on spermatozoa, and in different tissues of the male reproductive tract, but its function is not known. The aims of this study were to determine if the concentration of SAP in seminal plasma is associated with commonly assessed semen parameters and to investigate if SAP could be a new, indirect biomarker for these parameters. In a cross-sectional study of 203 young volunteers, the concentration of SAP in seminal plasma was measured with a in-house developed enzyme-linked immunosorbent assay. Scatter plots, Pearson's correlation coefficients (r), and linear regression models were produced, and SAP showed a statistically significant correlation with sperm concentration (r = 0.75), sperm number (r = 0.68), semen volume (r = -0.19), progressive sperm motility (r = 0.24), and sperm immotility (r = -0.20). When the study group was dichotomized, SAP could be used to discriminate samples with a sperm concentration < or ≥5 × 106 ml-1, 15 × 106 ml-1, or 40 × 106 ml-1, and in receiver operating characteristic curves, the corresponding areas under the curves were 0.97, 0.93, and 0.82, respectively, with P < 0.001 for all three cutoff values studied. The concentration of SAP in seminal plasma showed a strong, positive correlation with the concentration of spermatozoa in semen. SAP may be used as a new indirect potential biomarker for sperm concentration in fresh and in frozen, stored samples. In addition, it is envisaged that the assay could be developed into a home fertility test to differentiate between a low and a normal sperm concentration.

Combined analysis of serum SAP and PRSS2 for the differential diagnosis of CD and UC.

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic intestinal inflammatory disease. Crone's disease (CD) and ulcerative colitis (UC) are types of IBD. There is a need for a more accurate, noninvasive biomarker to distinguish CD from UC. PURPOSE: To verify the diagnostic value of combined serum trypsin 2 (PRSS2) and serum amyloid P component (SAP) evaluation in distinguishing CD from UC. METHODS: The subjects included 28 normal controls (NC) as well as 44 UC, 72CD, 16 colorectal cancer (CRC), 10 colorectal polyps, and 10 cancer cases. Serum SAP, PRSS2, CRP, and CEA were measured and compared. RESULTS: The concentration of CEA in CRC and other gastrointestinal tumors was significantly higher than that in UC, CD, and colorectal polyps. The concentration of CRP was significantly higher in UC and CD than that in the healthy group, but there were no significant differences when compared to the intestinal polyp group. Serum PRSS2 concentration was significantly higher in the UC and CD groups than that in the colorectal polyp group, and the average serum concentration of SAP in CD was significantly higher compared to UC. In patients with colorectal polyps, there was no correlation between PRSS2 and CRP. ROC curve analysis showed that the AUC of PRSS2 used to distinguish IBD patients from healthy controls or colorectal polyp patients was 0.730 and 0.774, respectively. The AUC of SAP used to distinguish CD from UC was 0.706. The AUC of combined PRSS2 and SAP was not different from the AUC for individual SAP. Finally, we demonstrated that the expression of SAP in CD patient tissues was significantly higher than that in UC patients. CONCLUSION: The combined analysis of serum SAP and PRSS2 has differential diagnostic value for CD and UC.

Relationship between serum SREBP-1, SAP and endocrine metabolism in patients with polycystic ovary syndrome / 中华内分泌外科杂志

Objective:To investigate the relationship between serum sterol regulatory element binding protein-1 (SREBP-1) , serum amyloid P (SAP) and endocrine metabolism in patients with polycystic ovary syndrome.Methods:75 patients with polycystic ovary syndrome (study group) and 70 healthy women (control group) admitted to the First People’s Hospital of Yuhang District from Mar. 2018 to Feb. 2020 were enrolled. Various indexes were detected in both groups, including body mass index (BMI) , SREBP-1, SAP, triglyceride (TG) , total cholesterol (TC) , high-density lipoprotein (HDL-C) , and low-density lipoprotein (LDL-C) , fasting blood glucose (FBG) , fasting insulin (FINS) , and insulin resistance index (HOMA-IR) . The study group was further divided into two subgroups according to BMI, overweight group and normal group. SREBP-1 and SAP were compared between the two groups. Pearson correlation analysis was used to analyze the correlation between SREBP-1, SAP, blood lipid index, blood glucose index and BMI in patients with polycystic ovary syndrome.Results:The body weight and BMI index of study group were higher than those of control group [ (72.23±4.84) kg vs (58.23±3.25) kg, (25.02±2.75) kg/m 2 vs (22.11±1.34) kg/m 2, P<0.05]. The levels of serum SREBP-1 and SAP in the study group were significantly higher than those in the control group [ (334.78±32.06) pg/ml vs (206.34±25.71) pg/ml, (206.34±25.71) mg/U vs (39.16 ±0.58) mg/U, P<0.05]. The expression levels of TG, TC, LDL-C, FBG, FINS, and HOMA-IR in the study group were higher than those in the control group [ (2.32±0.71) vs (1.53±0.52) , (4.85±0.54) vs (3.41±0.66) , (3.06±0.75) vs (2.11±0.89) , (6.45±0.62) vs (5.59±0.76) , (16.14±1.03) vs (13.02±1.34) , (1.67±0.38) vs (1.18± 0.26) , P<0.05]; HDL-C expression level in the study group was lower than that in the control group [ (1.43±0.56) vs (1.71±0.42) , P<0.05]. The levels of SREBP-1 and SAP in overweight group were higher than those in normal group [ (339.19±27.63) pg/ml vs (281.67±20.18) pg/ml, (53.26±0.59) mg/U vs (42.48±0.67) mg/U, P<0.05]. Serum SREBP-1 and SAP in the study group were positively correlated with TG, TC, LDL-C, HOMA-IR, and BMI, and were negatively correlated with HDL-C ( P<0.05) . Conclusion:SREBP-1 and SAP levels are elevated in patients with polycystic ovary syndrome, which are significantly correlated with TG, TC, LDL-C, HOMA-IR, BMI, and HDL-C, and can cause endocrine disorder by affecting glucose and lipid metabolism.

Serum amyloid P component: a new biomarker for low sperm concentration? / 亚洲男科学杂志(英文版)

Serum amyloid P component (SAP) is present in seminal plasma, on spermatozoa, and in different tissues of the male reproductive tract, but its function is not known. The aims of this study were to determine if the concentration of SAP in seminal plasma is associated with commonly assessed semen parameters and to investigate if SAP could be a new, indirect biomarker for these parameters. In a cross-sectional study of 203 young volunteers, the concentration of SAP in seminal plasma was measured with a in-house developed enzyme-linked immunosorbent assay. Scatter plots, Pearson's correlation coefficients (r), and linear regression models were produced, and SAP showed a statistically significant correlation with sperm concentration (r = 0.75), sperm number (r = 0.68), semen volume (r = -0.19), progressive sperm motility (r = 0.24), and sperm immotility (r = -0.20). When the study group was dichotomized, SAP could be used to discriminate samples with a sperm concentration < or ≥5 × 10

The Basic Characteristics of the Pentraxin Family and Their Functions in Tumor Progression.

The pentraxin is a superfamily of proteins with the same domain known as the pentraxin domain at C-terminal. This family has two subgroups, namely; short pentraxins (C-reactive protein and serum amyloid P component) and long pentraxins (neuronal pentraxin 1, neuronal pentraxin 2, neuronal pentraxin receptor, pentraxin 3 and pentraxin 4). Each group shares a similar structure with the pentameric complexes arranged in a discoid shape. Previous studies revealed the functions of different pentraxin family members. Most of them are associated with human innate immunity. Inflammation has commonly been associated with tumor progression, implying that the pentraxin family might also participate in tumor progression. Therefore, we reviewed the basic characteristics and functions of the pentraxin family and their role in tumor progression.